Induced production of a new dipeptide with a disulfide bridge by long-term fermentation of marine-derived Trichoderma cf. brevicompactum

Tetrahedron Letters
2016.0

Abstract

The marine-derived fungus Trichoderma sp. TPU199 (cf. T. brevicompactum), originally isolated from a Palauan red alga, was found to produce unprecedented epipolythiodiketopiperazines, such as gliovirin and pretrichodermamide A. Long-term static fermentation of the strain induced the production of a new dipeptide, dithioaspergillazine A (1), together with aspergillazine A (2) and three anthraquinones (3–5). The structure of 1 was identified as a modified dipeptide possessing a disulfide bridge based on spectroscopic data for 1 and comparisons with those for 2. On the other hand, long-term agitating fermentation of the strain led to the production of the known bisabolane-type sesquiterpene, (+)-12 hydroxysydonic acid (6), which formed the cyclic derivative 7 during HPLC purification under acidic conditions. Compound 1 exhibited cytotoxicity against HCT-15 and Jurkat cells with IC50 values of 13 and 1.3 lM, respectively. Compound 2 did not affect the proliferation of these cancer cells up to a concentration of 22 lM.

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